A Phase I/II Study of Vosaroxin and Decitabine in Older Patients With Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Vosaroxin in Combination With Decitabine
研究概览
简要总结
The goal of this clinical research study is to learn if the combination of vosaroxin and decitabine can help to control AML or MDS. The safety of these drugs will also be studied.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of up to 6 participants will be enrolled in the Phase I portion of the study, and up to 60 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of vosaroxin you receive will depend on when you joined this study. The first group of participants will receive the highest dose level of vosaroxin. If no intolerable side effects are seen, the study will move on to Phase II. If intolerable side effects are seen, each new group will receive a lower dose of vosaroxin than the group before it until the most tolerable dose is found.
If you are enrolled in the Phase II portion, you will receive vosaroxin at the highest dose that was tolerated in the Phase I portion.
All participants will receive the same dose level of decitabine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Previously untreated AML (>/= 20% blasts). Patients with high-risk MDS (defined as having >/= 10% blasts in the bone marrow) or patients with Chronic Myelomonocytic Leukemia (CMML) (having >/= 10% blasts in the bone marrow) may also be eligible after discussion with Principal Investigator (PI). Prior therapy with hydroxyurea, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed, however prior therapy with chemotherapy agents for the disease under study is not allowed. Patients may have received one dose of cytarabine (up to 2 g/m2) administered at presentation for control of hyperleucocytosis. For patients with prior MDS or CMML who transformed to AML, therapy received for MDS is not considered as prior therapy for AML.
- •Age >/= 60 years and not candidates for conventional cytotoxic chemotherapy or refuse it; OR patients below the age of 60 years who are considered unfit and/or unable to tolerate standard chemotherapy at the discretion of the treating physician or the principal investigator. "
- •Eastern Cooperative Oncology Group performance status </=
- •Adequate hepatic (serum total bilirubin </= 1.5 x upper limit normal (ULN), alanine aminotransferase and/or aspartate transaminase </= 2.5 x ULN) and renal function (creatinine </= 2.0 mg/dL).
- •Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
- •Patients must be willing and able to review, understand, and provide written consent before starting therapy.
- •Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum pregnancy test within 14 days before the start of the treatment. Women of childbearing potential may have a urine pregnancy test, instead of a serum pregnancy test. If either the serum or urine pregnancy test is equivocally negative the patient will be eligible for the protocol. Women of childbearing potential must agree to use an adequate method of contraception during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment.
排除标准
- •New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as active angina pectoris, clinically significant cardiac arrhythmia that requires therapy in the opinion of the treating physician or PI, uncontrolled hypertension (blood pressure > 160 systolic and > 110 diastolic not responsive to antihypertensive medication), uncontrolled diabetes mellitus in the opinion of the treating physician or PI, or uncontrolled congestive heart failure in the opinion of the treating physician or PI.
- •Myocardial infarction in the previous 12 weeks (from the start of treatment).
- •Active and uncontrolled disease/infection as judged by the treating physician
- •Pregnant or breastfeeding
- •Known Human Immunodeficiency Virus seropositivity
- •Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor
- •Acute promyelocytic leukemia (APL).
研究组 & 干预措施
Vosaroxin + Decitabine
The first 6 patients on study (first cohort) receive 1 or 2 induction cycles of therapy according to the following starting schedule: Vosaroxin administered intravenously on days 1 and 4 at a dose of 90 mg/m2 in the first cycle (induction 1) for a total dose of 180 mg/m2/cycle in combination with Decitabine at a dose of 20 mg/m2 intravenously daily for 5 consecutive days (Days 1 to 5).
Following the phase I portion, patients in phase II receive the following induction:
- Vosaroxin intravenously on days 1 and 4 at a dose of 70 mg/m2 for a total dose of 140 mg/m2/cycle (days 1 and 4), or the final induction dose (MTD) determined in phase I.
- Decitabine intravenously at a dose of 20 mg/m2 for 5 consecutive days (days 1 to 5), or the final induction dose (MTD) determined in phase I.
干预措施: Vosaroxin (Drug)
Vosaroxin + Decitabine
The first 6 patients on study (first cohort) receive 1 or 2 induction cycles of therapy according to the following starting schedule: Vosaroxin administered intravenously on days 1 and 4 at a dose of 90 mg/m2 in the first cycle (induction 1) for a total dose of 180 mg/m2/cycle in combination with Decitabine at a dose of 20 mg/m2 intravenously daily for 5 consecutive days (Days 1 to 5).
Following the phase I portion, patients in phase II receive the following induction:
- Vosaroxin intravenously on days 1 and 4 at a dose of 70 mg/m2 for a total dose of 140 mg/m2/cycle (days 1 and 4), or the final induction dose (MTD) determined in phase I.
- Decitabine intravenously at a dose of 20 mg/m2 for 5 consecutive days (days 1 to 5), or the final induction dose (MTD) determined in phase I.
干预措施: Decitabine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Vosaroxin in Combination With Decitabine
时间窗: 21 days
Maximum tolerated dose (MTD) defined as highest daily oral dose evaluated at which \<33% of patients experience a dose limiting toxicity (DLT). A non-hematologic dose-limiting toxicity (DLT) defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to CTCAE criteria) assessed by treating physician as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during the first 28 days on study. A hematologic DLT defined as severe myelosuppression with a hypoplastic marrow with less than 5% cellularity and no evidence of leukemia 42 days from start of therapy. This will define severe and delayed myelosuppression not related to persistent leukemia and likely related to treatment.
次要结局
- Participants With a Response(21 days)